Title

Authors

Document Type

Poster

Keywords

Drug Delivery; Ultrasound

Publication Date

4-2017

Abstract

INTRODUCTION

Onychomycosis is a fungal nail disorder that can be extremely painful. In onychomycosis, the fungus lives on the nail bed. Due to the poor permeability of the nail, current antifungal drugs, which are applied to the top of the nail, are unable to reliably reach the nail bed, making them ineffective in treating the fungus. The aim of our study has been to determine the effectiveness of using ultrasound to increase the permeability of the nail with the goal of improving outcomes in the treatment of onychomycosis.

MATERIALS AND METHODS

Porcine nails were used for all experiments. Two sets of ultrasonic experiments were performed. In both experiments, planar ultrasound transducers were used to sonicate the nails using frequencies of 400 kHz, 600 kHz, 800 kHz, and 1 MHz, an intensity of 1 +/- 0.1 W/cm2 and a duration of 5 min in continuous mode. In the first experiment, the luminosity experiment, a piece of porcine nail was placed in a beaker beneath the ultrasound transducer. The beaker was then filled with a drug-mimicking hydrophilic blue dye. After treatment, a microscopic image of the nails’ cross section was taken. This image was analyzed to compare the average brightness - and therefore permeation of dye. In the second experiment, the diffusion cell experiment, a Franz Diffusion Cell was used. The nail was placed above a receiving compartment filled with saline and the donor compartment was filled with the same blue dye. The nail was sonicated and the absorbance of the receiving compartment was measured to determine the permeation of dye through the nail. The final experiment was a safety modeling experiment performed using PZFlex software and a model of the human toe.

RESULTS AND DISCUSSION

In both the luminosity and diffusion cell experiments, the nails were found to have more permeation at higher frequencies. In the luminosity experiments (n=8 per group), the 600 kHz and 800 kHz frequencies were found to be statistically significant (p<0.05). The diffusion cell results found statistical significance (p<0.05) at 400 kHz, 600 kHz, 800 kHz and 1 MHz tests (n=6). In the temperature modeling experiment a safe temperature increase was found at all frequencies.

CONCLUSION

Our ongoing study efforts focus on testing the diffusion of an antifungal nail polish drug, ciclopirox, through the porcine nails. If proven successful our method may find a clinical application due to the non-invasive nature of proposed therapeutic ultrasound treatment.

Creative Commons License

Open Access

1

Comments

To be presented at GW Annual Research Days 2017.

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Ultrasound-enhanced Drug Delivery for Treatment of Onychomycosis

INTRODUCTION

Onychomycosis is a fungal nail disorder that can be extremely painful. In onychomycosis, the fungus lives on the nail bed. Due to the poor permeability of the nail, current antifungal drugs, which are applied to the top of the nail, are unable to reliably reach the nail bed, making them ineffective in treating the fungus. The aim of our study has been to determine the effectiveness of using ultrasound to increase the permeability of the nail with the goal of improving outcomes in the treatment of onychomycosis.

MATERIALS AND METHODS

Porcine nails were used for all experiments. Two sets of ultrasonic experiments were performed. In both experiments, planar ultrasound transducers were used to sonicate the nails using frequencies of 400 kHz, 600 kHz, 800 kHz, and 1 MHz, an intensity of 1 +/- 0.1 W/cm2 and a duration of 5 min in continuous mode. In the first experiment, the luminosity experiment, a piece of porcine nail was placed in a beaker beneath the ultrasound transducer. The beaker was then filled with a drug-mimicking hydrophilic blue dye. After treatment, a microscopic image of the nails’ cross section was taken. This image was analyzed to compare the average brightness - and therefore permeation of dye. In the second experiment, the diffusion cell experiment, a Franz Diffusion Cell was used. The nail was placed above a receiving compartment filled with saline and the donor compartment was filled with the same blue dye. The nail was sonicated and the absorbance of the receiving compartment was measured to determine the permeation of dye through the nail. The final experiment was a safety modeling experiment performed using PZFlex software and a model of the human toe.

RESULTS AND DISCUSSION

In both the luminosity and diffusion cell experiments, the nails were found to have more permeation at higher frequencies. In the luminosity experiments (n=8 per group), the 600 kHz and 800 kHz frequencies were found to be statistically significant (p<0.05). The diffusion cell results found statistical significance (p<0.05) at 400 kHz, 600 kHz, 800 kHz and 1 MHz tests (n=6). In the temperature modeling experiment a safe temperature increase was found at all frequencies.

CONCLUSION

Our ongoing study efforts focus on testing the diffusion of an antifungal nail polish drug, ciclopirox, through the porcine nails. If proven successful our method may find a clinical application due to the non-invasive nature of proposed therapeutic ultrasound treatment.